Thrombophilia, clinical factors, and recurrent venous thrombotic events

JAMA. 2005 May 18;293(19):2352-61. doi: 10.1001/jama.293.19.2352.


Context: Data on the recurrence rate of venous thrombotic events and the effect of several risk factors, including thrombophilia, remain controversial. The potential benefit of screening for thrombophilia with respect to prophylactic strategies and duration of anticoagulant treatment is not yet known.

Objectives: To estimate the recurrence rate of thrombotic events in patients after a first thrombotic event and its determinants, including thrombophilic abnormalities.

Design, setting, and patients: Prospective follow-up study of 474 consecutive patients aged 18 to 70 years without a known malignancy treated for a first objectively confirmed thrombotic event at anticoagulation clinics in the Netherlands. The Leiden Thrombophilia Study (LETS) was conducted from 1988 through 1992 and patients were followed up through 2000.

Main outcome measures: Recurrent thrombotic event based on thrombophilic risk factors, sex, type of initial thrombotic event (idiopathic or provoked), oral contraceptive use, elevated levels of factors VIII, IX, XI, fibrinogen, homocysteine, and anticoagulant deficiencies.

Results: A total of 474 patients were followed up for mean (SD) of 7.3 (2.7) years and complete follow-up was achieved in 447 (94%). Recurrence of thrombotic events occurred in 90 patients during a total of 3477 patient-years. The rate of thrombotic event recurrence was 25.9 per 1000 patient-years (95% confidence interval [CI], 20.8-31.8 per 1000 patient-years). The incidence rate of recurrence was highest during the first 2 years (31.9 per 1000 patient-years; 95% CI, 20.3-43.5 per 1000 patient-years). The risk of thrombotic event recurrence was 2.7 times (95% CI, 1.8-4.2 times) higher in men than in women. Patients whose initial thrombotic event was idiopathic had a higher risk of a thrombotic event recurrence than patients whose initial event was provoked (hazard ratio [HR], 1.9; 95% CI, 1.2-2.9). Women who used oral contraceptives during follow-up had a higher thrombotic event recurrence rate (28.0 per 1000 patient-years; 95% CI, 15.9-49.4 per 1000 patient-years) than those who did not (12.9 per 1000 patient-years; 95% CI, 7.9-21.2 per 1000 patient-years). Recurrence risks of a thrombotic event by laboratory abnormality ranged from an HR of 0.6 (95% CI, 0.3-1.1) in patients with elevated levels of factor XI to an HR of 1.8 (95% CI, 0.9-3.7) for patients with anticoagulant deficiencies.

Conclusions: Prothrombotic abnormalities do not appear to play an important role in the risk of a recurrent thrombotic event. Testing for prothrombotic defects has little consequence with respect to prophylactic strategies. Clinical factors are probably more important than laboratory abnormalities in determining the duration of anticoagulation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticoagulants / therapeutic use
  • Blood Coagulation Factors / analysis
  • Contraceptives, Oral
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Recurrence
  • Risk Factors
  • Thrombophilia / blood
  • Thrombophilia / physiopathology*
  • Venous Thrombosis / blood
  • Venous Thrombosis / epidemiology*
  • Venous Thrombosis / prevention & control


  • Anticoagulants
  • Blood Coagulation Factors
  • Contraceptives, Oral